nondestructive-monitoring-degradable-scaffold-based-tissue-engineered

Nondestructive Monitoring of Degradable Scaffold-Based Tissue-Engineered Blood Vessel Development Using Optical Coherence Tomography

Engineered vascular grafts with structural and mechanical properties similar to natural blood vessels are expected to meet the growing demand for arterial ...

Guangdong Academy of Medical Sciences, Guangdong General Hospital

The structural alterations in atrial myocytes appear to be an adaptive response of dedifferentiation during chronic atrial fibrillation (AF). Transcriptional activator ELK-1, one of the members of ETS family, has been shown to play an important role in regulating cell differentiation, It is reasonable to presume that ELK-1 participate in the molecular and structural remodeling by which AF is sustained. To prove this hypothesis, the expression of ELK-1 protein in chronically fibrillating atria compared to that in normal rhythmic atria was detected.

Downregulated protein expression of transcriptional activator ELK-1 in atrial myocardium of chronic AF patients.

Fibrosis, the hallmark of human injuries and diseases such as serious burns, is characterized by excessive collagen synthesis and myofibroblast accumulation. Transforming growth factor-β (TGF-β), a potent inducer of collagen synthesis, has been implicated in fibrosis in animals. In addition to TGF-β, fibroblast growth factor-inducible molecule 14 (Fn14) has been reported to play an important role in fibrotic diseases, such as cardiac fibrosis. However, the function and detailed regulatory mechanism of Fn14 in fibrosis are unclear. Here, we investigated the effect of Fn14 on the activation of human dermal fibroblasts. In normal dermal fibroblasts, TGF-β signaling increased collagen production and Fn14 expression. Furthermore, Fn14 siRNA blocked extracellular matrix gene expression; even when TGF-β signaling was activated by TGF-β1, fibroblast activation remained blocked in the presence of Fn14 siRNA. Overexpressing Fn14 increased extracellular matrix gene expression. In determining the molecular regulatory mechanism, we discovered that SMAD4, an important TGF-β signaling co-mediator, bound to the Fn14 promoter and activated Fn14 transcription. Taken together, these results indicate that the TGF-β signaling pathway activates Fn14 expression through the transcription factor SMAD4 and that activated Fn14 expression increases extracellular matrix synthesis and fibroblast activation. Therefore, Fn14 may represent a promising approach to preventing the excessive accumulation of collagen or ECM in skin fibrosis. 

Fn14, a Downstream Target of the TGF-β Signaling Pathway, Regulates Fibroblast Activation.

Non-destructive imaging strategies to monitor long-term cultures is essential for vascular engineering. The goal of this study is to investigate whether optical coherence tomography (OCT) can be a suitable approach to monitor the long-term remodeling process of biodegradable polymeric scaffold-based tissue-engineered vascular grafts (TEVG) after pulsatile stimulation and to observe polymeric scaffold degradation during bioreactor cultivation. In the present study, a perfusion system driven by a ventricular assist device was provided for a three-dimensional culture system as a pulsatile force. We characterized the structural features of wall thickness and polyglycolic acid degradation based on optical signal attenuation using catheter-based OCT. Scanning electron microscopy confirmed morphological changes. Also, polymer degradation and the detection of different types of collagen was visualized after 4 weeks of culture by means of polarized microscopy. Findings on OCT imaging correlated with those on histological examination and revealed the effects of pulsatile stimulation on the development of engineered vessels. This finding demonstrated that real-time imaging with OCT may be a promising tool for monitoring the growth and remodeling characterization of TEVG and provide a basis to promote the ideal and long-term culture of vascular tissue engineering.

In vitro remodeling and structural characterization of degradable polymer scaffold-based tissue-engineered vascular grafts using optical coherence tomography.

This study aimed to determine chromosomal abnormalities and copy number variations (CNVs) in fetuses with congenital heart disease (CHD) by chromosomal microarray analysis (CMA).

Clinical application of chromosomal microarray analysis for the prenatal diagnosis of chromosomal abnormalities and copy number variations in fetuses with congenital heart disease.

Article	Year
Downregulated protein expression of transcriptional activator ELK-1 in atrial myocardium of chronic AF patients. International journal of clinical and experimental pathology\| PubMed ID: 26617947	2015
Fn14, a Downstream Target of the TGF-β Signaling Pathway, Regulates Fibroblast Activation. PloS one\| PubMed ID: 26625141	2015
In vitro remodeling and structural characterization of degradable polymer scaffold-based tissue-engineered vascular grafts using optical coherence tomography. Cell and tissue research\| PubMed ID: 28887711	2017
Clinical application of chromosomal microarray analysis for the prenatal diagnosis of chromosomal abnormalities and copy number variations in fetuses with congenital heart disease. Prenatal diagnosis\| PubMed ID: 29573438	2018

Yueheng Wu

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